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Children whose mothers were treated for epilepsy who did not take folic acid during pregnancy were more likely to have autistic traits compared with those whose mothers took folic acid, a large Norwegian cohort study found.

Mothers treated with antiepileptic drugs who did not have periconceptional folic acid supplementation during pregnancy had a substantially increased risk of having offspring with autistic traits at age 18 months and 36 months, reported Marte Bjørk, MD, of Haukeland University Hospital in Norway, and colleagues.

Moreover, there was an inverse association between maternal plasma folate concentrations and folic acid doses during pregnancy and degree of autistic traits in children at age 3 years, they wrote in

They noted that children with exposure to antiepileptic drugs have of autistic traits, but that folic acid supplements are shown to of autism spectrum disorder in the But, they added, "to our knowledge, no previous studies have investigated whether this reduced risk also applies to children of women using [antiepileptic drugs]."

While they said that high-dose folic acid supplementation prior to pregnancy for users of antiepileptic drugs, they also acknowledged "the effect of the treatment "

Researchers examined prospective data from the population-based from June 1999 to December 2008. Pregnant women completed questionnaires twice during pregnancy and once when the child was 18 months and 36 months.

They noted that supplementary information was found through links to the , including information on antiepileptic drugs and folic acid supplementation. Autistic traits were measured with the and

Overall, complete information was available for 103,868 mothers. Mothers were a mean age of 29.4, and mean age was similar among women with epilepsy who were treated with antiepileptic drugs, women with epilepsy who were not treated with antiepileptic drugs, and women without epilepsy. There were 335 children who were exposed to antiepileptic drugs and 389 children whose mothers had untreated epilepsy.

Compared with children whose mothers used antiepileptic drugs and took folic acid during pregnancy, there was a substantial increased risk of children with autistic traits if their mothers had used these drugs with no periconceptional folic acid supplementation. This was seen among children at both 18 months (adjusted OR 5.9, 95% CI 2.2-15.8) and 36 months (adjusted OR 7.9, 95% CI 2.5-24.9), albeit with wide confidence intervals for both.

However, risks of autistic traits among offspring were only slightly increased among women without epilepsy who did not take folic acid during pregnancy (adjusted OR 1.3, 95% CI 1.2-1.4 at 18 months and adjusted OR 1.7, 95% CI 1.5-1.9 at 36 months, respectively). While there was an increased risk of autistic traits for offspring of women with untreated epilepsy and no folic acid supplementation at 36 months (adjusted OR 2.5, 95% CI 0.4-16.6), there was no increased risk of autistic traits for these children at 18 months (adjusted OR 1.0, 95% CI 0.4-3.0), despite wide confidence intervals.

In an , Kimford J. Meador, MD, of Stanford University in Stanford, California, said that the study "provides novel findings with important health care implications."

Meador noted that given half of pregnancies in this country are , and that the rate of unintended pregnancies among women with epilepsy, "women of childbearing potential should be advised to take folate supplements continuously," but cautioned that is needed to determine optimal doses for women taking antiepileptic drugs and the general population.

Study limitations included that the source was a single cohort, but that parental rating of autistic traits as opposed to a clinical evaluation may represent a limitation due to self-reporting of information.